Beneficial behavioral effects of chronic cerebral dopamine neurotrophic factor (CDNF) infusion in the N171-82Q transgenic model of Huntington's disease.

Huntington's disease (HD) is a progressive inherited neurological disease characterized by the degeneration of basal ganglia and the accumulation of mutant huntingtin (mHtt) aggregates in specific brain areas. Currently, there is no treatment for halting the progression of HD. Cerebral dopamine neurotrophic factor (CDNF) is a novel endoplasmic reticulum located protein with neurotrophic factor properties that protects and restores dopamine neurons in rodent and non-human primate models of Parkinson's disease. Our recent study showed that CDNF improves motor coordination and protects NeuN positive cells in a Quinolinic acid toxin rat model of HD. Here we have investigated the effect of chronic intrastriatal CDNF administration on behavior and mHtt aggregates in the N171-82Q mouse model of HD. Data showed that CDNF did not significantly decrease the number of mHtt aggregates in most brain regions studied. Notably, CDNF significantly delayed the onset of symptoms and improved motor coordination in N171-82Q mice. Furthermore, CDNF increased BDNF mRNA level in hippocampus in vivo in the N171-82Q model and BDNF protein level in cultured striatal neurons. Collectively our results indicate that CDNF might be a potential drug candidate for the treatment of HD.

Cerebral dopamine neurotrophic factor (CDNF) protects against quinolinic acid-induced toxicity in in vitro and in vivo models of Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder with a progressive loss of medium spiny neurons in the striatum and aggregation of mutant huntingtin in the striatal and cortical neurons. Currently, there are no rational therapies for the treatment of the disease. Cerebral dopamine neurotrophic factor (CDNF) is an endoplasmic reticulum (ER) located protein with neurotrophic factor (NTF) properties, protecting and restoring the function of dopaminergic neurons in animal models of PD more effectively than other NTFs. CDNF is currently in phase I-II clinical trials on PD patients. Here we have studied whether CDNF has beneficial effects on striatal neurons in in vitro and in vivo models of HD. CDNF was able to protect striatal neurons from quinolinic acid (QA)-induced cell death in vitro via increasing the IRE1α/XBP1 signalling pathway in the ER. A single intrastriatal CDNF injection protected against the deleterious effects of QA in a rat model of HD. CDNF improved motor coordination and decreased ataxia in QA-toxin treated rats, and stimulated the neurogenesis by increasing doublecortin (DCX)-positive and NeuN-positive cells in the striatum. These results show that CDNF positively affects striatal neuron viability reduced by QA and signifies CDNF as a promising drug candidate for the treatment of HD.

Imaging connected porosity of crystalline rock by contrast agent-aided X-ray microtomography and scanning electron microscopy.

We set out to study connected porosity of crystalline rock using X-ray microtomography and scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS) with caesium chloride as a contrast agent. Caesium is an important radionuclide regarding the final deposition of nuclear waste and also forms dense phases that can be readily distinguished by X-ray microtomography and SEM-EDS. Six samples from two sites, Olkiluoto (Finland) and Grimsel (Switzerland), where transport properties of crystalline rock are being studied in situ, were investigated using X-ray microtomography and SEM-EDS. The samples were imaged with X-ray microtomography, immersed in a saturated caesium chloride (CsCl) solution for 141, 249 and 365 days and imaged again with X-ray microtomography. CsCl inside the samples was successfully detected with X-ray microtomography and it had completely penetrated all six samples. SEM-EDS elemental mapping was used to study the location of caesium in the samples in detail with quantitative mineral information. Precipitated CsCl was found in the connected pore space in Olkiluoto veined gneiss and in lesser amounts in Grimsel granodiorite. Only a very small amount of precipitated CsCl was observed in the Grimsel granodiorite samples. In Olkiluoto veined gneiss caesium was found in pinitised areas of cordierite grains. In the pinitised areas caesium was found in notable excess compared to chloride, possibly due to the combination of small pore size and negatively charged surfaces. In addition, elevated concentrations of caesium were found in kaolinite and sphalerite phases. The findings concerning the location of CsCl were congruent with X-ray microtomography.

The role of surgery in Crohn's disease: a retrospective analysis from a single hospital.

BACKGROUND: Traditionally, in Crohn's disease (CD), surgery has played an essential role in the treatment of complications. TNF-α-blockers have significantly improved results of conservative treatment but they do not definitely cure Crohn's disease. AIM: Our aim was to examine the prevalence of and indications for surgical procedures in CD in our hospital. MATERIAL AND METHODS: A retrospective survey included all CD patients diagnosed in our hospital referral area during a 10-year period in 1996-2005. RESULTS: Altogether 114 new patients with CD were diagnosed, 56 (49%) males, 58 (51%) fe-males. The median follow-up time was 5.0 years. In all, 31 (27%) patients underwent some sur-gical procedure, and of these, 12 (39%) underwent an emergency operation. The most common indication for surgery was bowel obstruction. The most frequent procedures were ileocolic re-section in 12 (39%) patients and small bowel resection in 10 (32%). CONCLUSIONS: Almost one-third of CD patients needed surgical therapy in an early phase of their disease, and more than one-third of these underwent an emergency procedure. Obstructive symptoms were the most common indication for surgery in the early phase of CD.

The changing epidemiology of esophageal cancer in Finland and the impact of the surveillance of Barrett's esophagus in detecting esophageal adenocarcinoma.

We examined the epidemiology of esophageal cancer in Finland and the role of the surveillance of Barrett's esophagus (BE) in detecting esophageal adenocarcinoma (EA) in our own hospital referral area. We observed that the incidence of EA in men has increased tenfold from the 1970s and was 1.10/100,000/year in 1998-2002. In women, a 4.5-fold increase was observed (incidence 0.11/100,000/year). In 1998-2002, the mean annual number of new EA cases was 57.4 (79.8% men) in Finland with a population of 5.2 million. In our hospital referral area with a mean population of 261 349, 11 EAs were observed in 1996-2001. Of them, two (18.2%) had BE. One EA was detected during surveillance. EA comprised 0.05% of all causes of deaths in our hospital referral area. We conclude that EA incidence has increased significantly in men in Finland, but still EA is seldom detected on BE surveillance. EA is an uncommon cause of death in our hospital referral area.

Is it possible to reduce endoscopy workload using age, alarm symptoms and H. pylori as predictors of peptic ulcer and oesophagogastric cancers?

OBJECTIVES: We examined referrals to oesophagogastroduodenoscopy and the impact of demographic and clinical variables to predict major findings (peptic ulcer, cancer) on oesophagogastroduodenoscopy. METHODS: We collected data on 3669 consecutive patients referred for oesophagogastroduodenoscopy. RESULTS: Dyspeptic and reflux symptoms constituted 80% of oesophagogastroduodenoscopy referrals. A major finding was observed in 419 patients (11.4%). The mean age of cancer patients was 72.7 years (95% confidence interval (CI) 70.0-76.5 years) and that of peptic ulcer patients 62.0 years (95% CI 60.5-63.5 years). Independent risk factors for a major finding were age >50 years (odds ratio (OR) 1.62, 95% CI 1.24-2.10), male sex (OR 1.38, 95% CI 1.11-1.72), ulcer-type pain (OR 2.33, 95% CI 1.80-3.02), weight loss (OR 1.70, 95% CI 1.14-2.53), anaemia (OR 1.82, 95% CI 1.38-2.40), bleeding symptoms (OR 3.27, 95% CI 2.26-4.75) and Helicobacter pylori (OR 2.49, 95% CI 2.00-3.11), whereas reflux symptoms were protective (OR 0.73, 95% CI 0.53-1.00). The area under receiver operating characteristic curve of age over 50 years with alarm symptoms to predict major finding was 0.68 (95% CI 0.65-0.71), which positive H. pylori status increased to 0.71 (95% CI 0.69-0.74). Of the major findings, 87.2% were detected in patients with risk factors. Major findings were detected in 15.1% patients with and 8.1% (p < 0.001) without alarm symptoms. CONCLUSIONS: Dyspeptic and reflux symptoms constitute the majority of oesophagogastroduodenoscopy workload. Discriminative power of alarm symptoms even with positive H. pylori status to detect peptic ulcer or cancer was low. Because of their low cancer risk, reflux and dyspeptic patients younger than 50 years can be treated without oesophagogastroduodenoscopy.

The clinical value of taking routine biopsies from the incisura angularis during gastroscopy.

BACKGROUND AND STUDY AIMS: The incisura angularis is considered to be a typical site for Helicobacter pylori colonization, glandular atrophy, intestinal metaplasia, gastric ulcer, and gastric carcinoma. Our aim was to clarify whether it is necessary to biopsy the incisura angularis routinely during gastroscopy, in addition to obtaining biopsies of the corpus and antrum. PATIENTS AND METHODS: A total of 272 consecutive patients, with a mean age +/- SD of 53.8 +/- 15.5 years, had two biopsies taken from the angulus, two from the antrum, and two from the corpus of the stomach during routine upper gastrointestinal endoscopy. Histological specimens were examined according to the updated Sydney System for the classification and grading of gastritis. RESULTS: Of the 272 patients, 11 (4.0 %) showed chronic inflammation in the angulus biopsy only. Similarly, the angulus was the only biopsy site which showed neutrophil polymorph infiltration (or "activity") in two patients (0.7 %), intestinal metaplasia in 13 patients (4.7 %), atrophy in three patients (1.1 %), and H. pylori colonization in one patient (0.4 %). Dysplasia (intraepithelial neoplasia) was not found in any of the biopsied sites in any of the 272 patients. H. pylori was found in 39 of the 272 patients (14 %). Of the 272 patients, 120 patients showed abnormalities at the incisura angularis, 101 having gastropathy or erosions, and only 19 showing more specific macroscopic changes, the main ones being ulcer, ulcer scarring, and atrophy. Of the 152 patients with a normal-looking mucosa at the angulus, only six (3.9 %) showed the histological changes of chronic inflammation in the angulus alone. Similarly, the angulus was the only biopsy site which showed neutrophil polymorph infiltration in one patient (1/152, 0.7 %), and intestinal metaplasia in five patients (5/152, 3.3 %). Atrophy and H. pylori colonization were not seen exclusively at the angulus in any of the patients with a macroscopically normal-looking angulus. CONCLUSION: Based on our data, routine biopsy of the incisura angularis would provide little additional clinical information to that obtainable from antrum and corpus biopsies.

First-line eradication therapy for Helicobacter pylori in primary health care based on antibiotic resistance: results of three eradication regimens.

AIM: To determine the efficacy of three Helicobacter pylori eradication regimens and factors affecting the eradication results in Finland. METHODS: A total of 342 H. pylori-positive adult patients from primary health care referred for gastroscopy at 23 centres in different parts of Finland were randomized to receive either (i) lansoprazole 30 mg b.d., amoxicillin 1 g b.d. and metronidazole 400 mg t.d.s. (LAM), (ii) lansoprazole 30 mg b.d., amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. (LAC), or (iii) ranitidine bismuth citrate 400 mg b.d., metronidazole 400 mg t.d.s. and tetracycline 500 mg q.d.s. (RMT). A (13)C-urea breath test was performed 4 weeks after therapy. RESULTS: The eradication result could be assessed in 329 cases. Intention-to-treat cure rates of LAM, LAC, and RMT were 78, 91 and 81%. The difference was significant between LAM and LAC (P = 0.01) and between LAC and RMT (P = 0.04). The eradication rates in cases with metronidazole-susceptible vs. -resistant isolates were for LAM 93% vs. 53% (P = 0.00001), for LAC 95% vs. 84%, and for RMT 91% vs. 67% (P = 0.002). Previous antibiotic use, smoking, and coffee drinking reduced the efficacy of therapy. CONCLUSIONS: In unselected patients in primary health care, LAC was the most effective first-line eradication.

A survey of open-access endoscopy in primary health care centres: outcome of gastric carcinoma patients diagnosed by general practitioners compared with hospital-referred endoscopy.

BACKGROUND: We examined open-access endoscopy service based on general practitioner endoscopists. METHODS: We compared the survival of the gastric carcinoma patients originally diagnosed in health care centres by general practitioner endoscopists and hospital outpatient clinic by specialists. RESULTS: A total of 159 gastric carcinoma cases diagnosed during 1996-2000 were included in to the present study. Of them, 58% (N = 92) and 42% (N = 67) were detected by general practitioners and specialists, respectively. We observed no difference in the mean age of patients (71.3 years versus 71.4 years, p = 0.97) and stage of tumours [15% (N = 14) versus 21% localised tumours (N = 14, p = 0.30)] between cases diagnosed by general practitioners and specialists. The number of patients who underwent radical extirpation were 14% (N = 13) and 19% (N = 13, p = 0.38), respectively. After a minimum follow-up of 3.5 years, 29 patients (18%) were alive. The mean survival time of hospital-diagnosed carcinoma patients was longer (23.6 months versus 18.7 months, p = 0.23). Eight patients had undergone hospital-referred gastroscopy less than 3 years before cancer diagnosis. In multivariate analysis, radical extirpation of carcinoma (odds ratio 0.11, 95% confidence interval 0.04-0.28) predicted survival; whereas age (odds ratio 1.03 per year, 95% confidence interval 0.99-1.07 per year), female sex (odds ratio 1.785, 95% confidence interval 0.71-4.81) and the open-access endoscopy based on general practitioner endoscopists (odds ratio 1.48, 95% confidence interval 0.60-3.65) predicted neither survival nor carcinoma-related death. CONCLUSION: No significant difference was detected in the outcome of gastric cancer patients diagnosed in primary care centres by general practitioner endoscopists and in hospital outpatient clinic by specialists.

Primary Helicobacter pylori resistance to metronidazole and clarithromycin in the Finnish population.

AIM: To systematically determine Helicobacter pylori primary antimicrobial resistance in Finland and the associated demographic and clinical features. METHODS: A total of 342 adult patients referred for gastroscopy at 23 centres in different parts of Finland and positive for the rapid biopsy urease test were recruited. Clinical and demographic data were collected via a structured questionnaire. Patients with positive H. pylori culture and successful antibiotic sensitivity determination by the E-test method (n = 292) were included in the present analysis. RESULTS: The study population consisted of 134 men and 158 women, mean age 56 years (95% CI, 55-58 years). Resistance to metronidazole was 38% (110 of 292) and to clarithromycin 2% (seven of 292). Resistance to metronidazole was higher in women than in men (48% vs. 25%, P < 0.001). Previous use of antibiotics for gynaecological infections predicted metronidazole resistance (P = 0.01), and previous use of antibiotics for respiratory (P = 0.02) and dental infections (P = 0.02) the clarithromycin resistance. We observed no major geographical variations in metronidazole resistance. CONCLUSIONS: The primary metronidazole resistance of H. pylori was 38% and was common in women previously treated for gynaecological infections. Primary clarithromycin resistance was uncommon (2%) and may associate with previous dental and respiratory infections.

Open-access gastroscopy in primary health-care offices to prevent peptic ulcer-related hospitalization and mortality.

BACKGROUND: Open-access gastroscopy performed by general practitioners is available at some primary care health centres in our Central Finland hospital referral area. The aim of the present study was to examine whether this practice influences peptic ulcer-related hospitalization and mortality. METHODS: Data on peptic ulcer-related hospitalization were obtained from discharge registries of the hospitals. Cause of death statistics were obtained from Statistics Finland Bureau. RESULTS: In 1996--2001, 896 inhabitants living in our hospital referral area were hospitalized owing to peptic ulcer. Of these, 265 (29.6%) had an ulcer related to the use of aspirin (ASA) or non-steroidal anti-inflammatory drugs (NSAIDs). Among the hospitalized patients, mortality was 11.6% (n = 104). In municipalities with or without an open-access gastroscopy service, the rates of hospitalization were 49.1 cases/100,000/year (95% CI 44.8-53.4) versus 77.5 cases/100,000/year (95% CI 72.0-83.0), and ulcer-related mortality 5.6 cases/100,000/year (95% CI 4.1-7.1) versus 9.4/100,000/year (95% CI 7.5-11.3). In municipalities without the service, inhabitants were older and their overall morbidity and mortality higher than in municipalities offering open-access gastroscopy. Of patients under 75 years of age (n = 582), 48 (8.2%) died, compared with 56 (17.8%, P < 0.001) of patients aged 75 years or older (n = 314). Age was the only independent risk factor for death (odds ratio (OR) 1.03 per year (95% CI 1.02-1.05)). Among patients with ASA-NSAID-related ulcer, open-access endoscopy was protective against ulcer-related death (OR 0.17 (95% CI 0.03-0.85)). CONCLUSIONS: Open-access gastroscopy in primary health-care offices significantly reduces ASA-NSAID-related ulcer mortality and may also reduce overall ulcer-related hospitalizations. The present results may, however, be biased by demographic factors. Age is a risk factor for death during ulcer-related hospitalization.

Gastric metaplasia and chronic inflammation at the duodenal bulb mucosa.

BACKGROUND: Chronic inflammation and gastric metaplasia are often observed in biopsy specimens from the duodenal bulb of Heliobacter pylori positive patients with duodenal ulcer disease (DU). AIMS: We set out to investigate the prevalence of these lesions and their associations with other gastric and duodenal histopathological lesions. PATIENTS: A total of 1255 consecutive patients who underwent upper gastrointestinal endoscopy were recruited into the present study. METHODS: Two biopsy specimens were obtained from each of the following sites: duodenal bulb, gastric antrum, gastric body, and distal to the superior duodenal angle. These specimens were stained with hematoxylin-eosin, alcian blue periodic acid Schiff (pH 2.5) and modified Giemsa (Heliobacter pylori infection was determined only by histology). RESULTS: The mean age of the study population was 57 years, and male:female ratio 1:1.6. Overall, 235 (19%) had gastric metaplasia and/or chronic inflammation in the duodenal bulb mucosa, and H. pylori organisms could be found in 17 (1%). In univariate analyses, gastric metaplasia and/or chronic duodenal bulb inflammation positively associated with male sex (p = 0.046), Heliobacter pylori-positive chronic gastritis (p = 0.033), villous atrophy of distal duodenal mucosa, i.e., coeliac disease (p < 0.001), duodenal ulcer (p < 0.001), and duodenal bulb deformity and scarring in endoscopy (p < 0.001), but not with age (p = 0.7) nor use of nonsteroidal anti-inflammatory drugs (p = 0.055). Multivariate analysis revealed that independent risk factors for gastric metaplasia and chronic inflammation in duodenal bulb were duodenal Heliobacter pylori infection (odds ratio 1.6, 95% confidence interval CI 1.1-2.1), and villous atrophy of the distal duodenal mucosa (odds ratio 12.7, 95% CI 4.4-36.5), while chronic atrophic gastritis was protective against them (odds ratio 0.5, 95% CI 0.3-0.8). CONCLUSIONS: In addition to Heliobacter pylori infection, duodenal bulb gastric metaplasia and chronic inflammation may result from predisposition to toxic dietary components in gluten-sensitive subjects.

Impact of clinical symptoms and referral volume on endoscopy for detecting peptic ulcer and gastric neoplasms.

BACKGROUND: We investigated the volume of dyspeptic patients referred by general practitioners (GPs) to upper gastrointestinal endoscopy and the impact on endoscopic findings. We also examined the correlation between clinical symptoms and endoscopic findings. METHODS: We collected data on patients sent for upper gastrointestinal endoscopy by GPs of 30 healthcare centres in 1996 in our hospital referral area of 260,000 inhabitants. In addition, national and local cancer registries were used to enumerate the gastric cancer cases detected in 1996. RESULTS: The study population consisted of 3378 patients, mean age 58 years (interquartile range 25 years, male:female 1:1.3). Among the 30 healthcare centres, referral volumes for upper gastrointestinal endoscopy varied from 0.6 to 9.2 per 1000 inhabitants per year (median 3.3/1000/year). In healthcare units with 'high' (> or = 3.3/1000/year, 15 healthcare units, 1297 patients) and 'low' (<3.3/1000/year, 15 healthcare units, 2065 patients) referral volumes, the detection rates were as follows: duodenal ulcer (DU) 3.5% (n = 46) versus 4.0% (n = 83, P = 0.5), gastric ulcer (GU) 4.9% (n = 64) versus 5.3% (n = 110, P = 0.6), gastropathy 43.8% (n = 568) versus 35.6% (n = 736, P < 0.001), gastric cancer 0.5% (n = 6) versus 0.5% (n = 11, P = 0.8), gastric polyps 2.4% (n = 31) versus 1.5% (n = 30, P < 0.05). Independent risk factors for gastric cancer were age (OR 6.5 per decade, 95% CI 2.4-17.9), male sex (OR 5.5, 95% CI 1.8-17.1) and alarming symptoms and/or signs (OR 3.6, 95% CI 1.2-10.7); for GU, Helicobacter pylori (OR 2.6, 95% CI 1.9-3.5) and alarming symptoms (OR 2.0, 95% CI 1.4-2.7); for DU, male sex (OR 1.6, 95% CI 1.1-2.2) and H. pylori (OR 3.9, 95% CI 2.7-5.5); and for gastric polyp(s), age (OR 2.0 per decade, 95% CI 1.1-3.5) and high referral volume (OR 1.7, 95% CI 1.0-2.0). A high referral volume did not associate positively either with the number of peptic ulcers or gastric cancer. CONCLUSIONS: Alarm symptoms associate strongly with significant gastric lesions such as GU and cancer. Increased referral volume results in an increased number of gastropathy and gastric polyp(s), but not of peptic ulcer or cancer.

Immunohistochemical study of neuroendocrine cells at the gastric cardia mucosa.

BACKGROUND/AIMS: The gastric cardia mucosa is a narrow band of tissue between the oesophagus and the stomach. The physiological role of this tissue is unknown. This study examined the presence and characteristics of neuroendocrine cells at this site. METHODS: Biopsy samples were obtained from across normal appearing squamocolumnar junctions. The cardiac mucosa was defined as the presence of special type mucosa composed of mucous secreting glands in the immediate vicinity of oesophageal squamous epithelium. Biopsy specimens were stained with haematoxylin and eosin, alcian blue (pH 2.5) periodic acid Schiff, and modified Giemsa. The chromogranin A and Fontana-Masson stains were used to identify neuroendocrine cells, which were also stained immunohistochemically for gastrin, serotonin, glucagon, pancreatic polypeptide, somatostatin, and vasoactive intestinal peptide. RESULTS: Chromogranin positive cells were seen in 18 cases with adequate biopsy specimens from the gastric cardia mucosa. These cells were all serotonin positive, but stains for other peptide hormones remained negative. Serotonin positive cells were detected only at the base of foveolae at the periphery of mucous secreting cardiac glands, giving a microscopic appearance resembling that of endocrine cells at the gastric antrum. The presence and numbers of serotonin positive cells did not correlate with chronic inflammation or intestinal metaplasia of the cardiac mucosa. These cells were seen both in Helicobacter pylori positive and negative patients. CONCLUSIONS: Serotonin positive cells appear to be the sole neuroendocrine cell type at the gastric cardia mucosa. These cells may have a role in regulating the physiology of the gastric cardia mucosa and the lower oesophageal sphincter.

Foveolar hyperplasia at the gastric cardia: prevalence and associations.

AIMS: In the gastric antrum and body, foveolar hyperplasia is a feature of reactive gastritis resulting from--for example, duodenogastric bile reflux and the use of non-steroidal anti-inflammatory drugs (NSAIDs). The aim of this study was to examine the occurrence and clinical relevance of gastric cardiac foveolar hyperplasia. METHODS: The study population was drawn from a consecutive series of 1698 patients sent for upper gastrointestinal endoscopy. Only cases without chronic gastritis or Barrett's oesophagus were included. The final study population consisted of 307 patients. RESULTS: Foveolar hyperplasia was seen in the gastric cardiac mucosa in 31 (10%) patients with histologically normal stomach mucosa, but none had endoscopically noticeable hyperplastic polyps. Compared with patients without gastric cardiac hyperplasia, those with hyperplasia more often had chronic inflammation and complete intestinal metaplasia in the junctional biopsies (48% v 77% and 9% v 26%, respectively). Logistic regression analysis revealed that chronic cardiac inflammation (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.3 to 7.8) and intestinal metaplasia of the complete type (OR, 2.8; 95% CI, 1.1 to 7.1) were independent risk factors for cardiac foveolar hyperplasia. In univariate analysis, endoscopic erosive oesophagitis (endoscopy positive gastro-oesophageal reflux disease) and the use of NSAIDs were not related to the presence of foveolar hyperplasia. CONCLUSIONS: Foveolar hyperplasia in the gastric cardiac mucosa occurs in patients with histologically normal non-gastritic stomachs and may develop as a consequence of chronic inflammation limited to the gastro-oesophageal junction ("junctitis"). It is not associated directly with endoscopy positive gastro-oesophageal reflux disease or the use of NSAIDs.

Impact of non-steroidal anti-inflammatory drug and aspirin use on the prevalence of dyspepsia and uncomplicated peptic ulcer disease.

BACKGROUND: Non-steroidal anti-inflammatory drug and aspirin (here collectively called NSAIDs) use is the second most common aetiologic factor for peptic ulcer disease and a major factor for peptic ulcer complications. The role of NSAIDs in the pathogenesis of uncomplicated peptic ulcer is less well understood and the interaction between NSAIDs and Helicobacter pylori infection on ulcer development is controversial. The aim of the present study was to examine the role of NSAIDs in the occurrence and clinical features of uncomplicated peptic ulcer disease. METHODS: A total of 1091 consecutive patients referred for open-access upper gastrointestinal endoscopy by general practitioners (GPs) were enrolled. The use of NSAIDs was gathered from a structured questionnaire completed by the patients and from patient files by GPs. The exclusion criteria were previous H. pylori eradication and gastric surgery, as well as symptoms and/or signs suggestive of acute gastrointestinal bleeding. RESULTS: Of the whole study group (n = 1091), 76 (7%) patients had a peptic ulcer. Thirty patients had an NSAID-use-associated peptic ulcer and 46 patients a non-NSAID-use peptic ulcer. Of patients with chronic gastritis (n = 599), 71% were H. pylori-positive and 108 used NSAIDs. Of those with chronic gastritis, 23 had an NSAID-use-associated peptic ulcer and 38 a non-NSAID ulcer. Of patients with normal gastric histology (n = 492), 75 patients used NSAIDs, 7 had an NSAID ulcer and 8 a non-NSAID ulcer. The only independent risk factor for peptic ulcer in patients using NSAIDs was H. pylori infection (odds ratio (OR) 3.1, 95% confidence interval (CI) 1.3-7.3), whereas dyspepsia (OR 1.0, 95% CI 0.4-2.4), male sex (OR 1.4, 95% CI 0.6-3.4), age (OR 1.0 per decade, 95% CI 0.8-1.3) and anaemia (OR 2.9, 95% CI 0.9-8.7) were not risk factors. In patients not using NSAIDs, independent risk factors for peptic ulcer were dyspepsia (OR 4.3, 95% CI 2.1-8.8), male sex (OR 2.0, 95% CI 1.1-2.8), age (OR 1.2 per decade, 95% CI 1.0-1.5), anaemia (OR 6.2, 95% CI 2.6-14.9) and H. pylori infection (OR 7.5, 95% CI 3.4-16.6). When comparing patients using NSAIDs or not, the OR of patients on NSAIDs for peptic ulcer was 2.7 (95% CI 1.5-5.0) among patients with chronic H. pylori gastritis (n = 424) and 5.3 (95% CI 1.8-15.0) among patients with normal gastric mucosa (n = 492). CONCLUSIONS: The use of NSAIDs increases the risk of peptic ulcer 3- and 5-fold in H. pylori-positive and H. pylori-negative patients, respectively. Dyspepsia is a poor predictor of peptic ulcer among patients using NSAIDs, and serologic H. pylori testing and treatment for chronic NSAID users is recommended.

Inflammation in the cardia.

The detection of chronic inflammation and intestinal metaplasia at the gastric side of a normal-appearing esophagogastric junction started active research on gastric cardia pathology. The main causes for this interest have been the increasing incidence of gastroesophageal reflux disease (GERD) and cardia adenocarcinoma. Many controversies still exist. It is even controversial whether noninflamed gastric cardia epithelium is a normal structure present at birth or an acquired lesion as a consequence of GERD. Similarly, the pathogenesis of chronic inflammation and intestinal metaplasia of gastric cardia are a matter of debate. Some researchers consider these lesions to be a consequence of Helicobacter pylori infection, whereas others think that chronic cardia inflammation and intestinal metaplasia are consequences of GERD. In this paper we review recent published studies in this field.

Classical Barrett esophagus contrasted with Barrett-type epithelium at normal-appearing esophagogastric junction. Central Finland Endoscopy Study Group.

BACKGROUND: Incomplete intestinal metaplasia or specialized columnar epithelium (SCE) is the histologic hallmark of Barrett esophagus (BE), but it may also occur at a normal-appearing gastroesophageal junction without BE. We studied whether differences occur between BE patients and those with SCE at the squamocolumnar junction but without BE (abbreviated JSCE), in terms of endoscopic and histologic signs of gastroesophageal reflux disease (GERD) and Helicobacter pylori gastritis. METHODS: A total of 1059 consecutive patients referred for endoscopy in one hospital district in Finland were enrolled in the study. Biopsy specimens (at least two from each site) were obtained from the gastric antrum and the corpus of the stomach and from the esophagogastric junction and distal esophagus. RESULTS: Classical BE was detected in 25 (2%) and JSCE in 99 (9%) patients. Dysplasia in the metaplastic mucosa was observed in six BE patients but in none of the JSCE patients (P < 0.001). In multivariate analysis the independent risk factors for BE were endoscopic erosive esophagitis (odds ratio (OR), 6.08; 95% confidence interval (CI), 2.50-14.82), male sex (OR, 3.02; 95% CI, 1.20-7.65), and age (OR, 1.02 per year; 95% CI, 1.00-1.06). The independent risk factors for JSCE were endoscopic erosive esophagitis (OR, 1.88; 95% CI, 1.08-3.29) and age (OR, 1.03; 95% CI, 1.02-1.05) but not H. pylori infection (OR, 1.57; 95% CI, 0.83-2.97) or chronic gastritis (OR, 0.88; 95% CI, 0.44-1.75). In univariate analysis, however, JSCE was associated with antral-predominant atrophic gastritis (77% H. pylori-positive). Unlike in JSCE patients, male sex strongly predominated among BE patients (P = 0.01). The mean ages of BE and JSCE patients did not differ. CONCLUSIONS: Both BE and JSCE without BE increase in prevalence with age, and both associate with endoscopic erosive esophagitis but not with H. pylori gastritis. However, because of the marked sex disparity, JSCE cannot be a direct precursor of BE, and some factors other than GERD alone also play a role in the pathogenesis of BE. Compared with BE, dysplasia is a rare finding in JSCE, and endoscopic surveillance with biopsy specimens from JSCE patients without dysplasia is not recommended.

Gastroesophageal reflux disease: prevalence, clinical, endoscopic and histopathological findings in 1,128 consecutive patients referred for endoscopy due to dyspeptic and reflux symptoms.

BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) reportedly has increased in prevalence while Helicobacter pylori infection and peptic ulcer disease have been on the decrease. The aim of the present study was to examine the prevalence of GERD as well as the clinical, endoscopic and histologic variables that associate with GERD in patients referred for endoscopy. PATIENTS AND METHODS: The study population was drawn from 1,562 consecutive patients referred for endoscopy. The exclusion criteria were previous H. pylori eradication, gastric surgery, anemia and weight loss. Thus 1,128 patients were enrolled in the present study. RESULTS: Of the 1,128 patients, 199 (18%) were referred for endoscopy due to heartburn and/or regurgitation. GERD, defined as chronic (>6 months) heartburn and/or regurgitation with or without erosive esophagitis, Barrett's esophagus, esophageal ulcer or stricture, was detected in 248 (22%) patients. Of the 248 GERD patients, 81 (33%) had endoscopy-negative GERD, but of those aged <50 years (n = 67), 57 (85%) were endoscopy-negative. The overall incidence of GERD was 307 per 100,000 population/year and that of endoscopy-positive GERD 207/100,000/year. The positive and negative predictive values of heartburn and regurgitation for endoscopy-positive GERD were 0.37 (95% CI 0.31-0.44) and 0.90 (95% CI 0.88-0.92), respectively. Independent risk factors for GERD were male sex (OR 1.9, 95% CI 1.3-2.7), previous medication for upper gastrointestinal symptoms (OR 2.7, 95% CI 1.7-4.1), the use of nonsteroidal anti-inflammatory drugs (NSAIDs; OR 2.0, 95% CI 1.3-3. 0), histologic esophagitis (OR 2.2, 95% CI 1.5-3.2) and incomplete intestinal metaplasia at the gastroesophageal junction (OR 1.7, 95% CI 1.0-3.1). Chronic gastritis was protective against GERD (OR 0.7, 95% CI 0.5-0.9). No association was observed between GERD and H. pylori infection. The risk of patients aged <50 years (n = 407) of having major lesion (Barrett's esophagus, esophageal stricture, peptic ulcer, esophageal/gastric carcinoma) was significantly lower than that of patients aged >50 years (n = 721; OR 0.5, 95% CI 0.3-0. 9, p = 0.01). CONCLUSIONS: The correlation between reflux symptoms and endoscopy-positive GERD is poor and most GERD patients aged <50 years have endoscopy-negative GERD. The use of NSAIDs is a risk factor for GERD, whereas chronic gastritis, but not H. pylori infection, may protect against GERD. Incomplete intestinal metaplasia at the gastroesophageal junction is associated with GERD.